During refrigerated storage leukocytes in donor blood progressively undergo apoptosis followed by secondary necrosis. Using an inbred rodent transfusion model, recipient animals received viable, necrotic, or apoptotic cells. While transfusion of viable blood MNCs stimulated production of IgM, IgG1 (Th2 type) and IgG2a (Th1-type) antidonor antibodies, leading to a suppression of subsequent DTH to donor antigens, transfusion of apoptotic donor cells led to neither alloimmunization nor immunosuppression. On the other hand transfusion of lysed donor cells resulted in production of IgM and IgG1 (Th2-type) antidonor antibodies and to a strong suppression of subsequent DTH to donor antigens. Intravenously administered spleen cells that had been depleted of professional APCs and enriched for B cells stimulated IgM antidonor antibodies but not IgG antibodies. Transfusion of such cells also led to suppression of subsequent DTH to donor antigens, probably through induction of anergy or apoptosis in alloantigen-reactive recipient cells. Depending on the duration of blood storage any or all of these 4 classes of cells may be present and Th2 and/or Th1 effector mechanisms can be generated following blood transfusion.